Prostate Cancer Epithelial Mesenchymal Transition by TGF-ß1 exposure monitored with a Photonic Crystal Biosensor.

During prostate cancer progression, cancerous epithelial cells can undergo epithelial-mesenchymal transition (EMT). EMT is a crucial mechanism for the invasion and metastasis of epithelial tumors characterized by the loss of cell-cell adhesion and increased cell mobility. It is associated with biochemical changes such as epithelial cell markers E-cadherin and occludins being down-regulated, and mesenchymal markers vimentin and N-cadherin being upregulated. These changes in protein expression, specifically in the cell membrane, may be monitored via biophysical principles, such as changes in the refractive index (RI) of the cell membrane. In our previous research, we demonstrated the feasibility of using cellular RI as a unique contrast parameter to accomplish label-free detection of prostate cancer cells. In this paper, we report the use of our Photonic-Crystal biosensor in a Total-Internal-Reflection (PC-TIR) configuration to construct a label-free biosensing system, which allows for ultra-sensitive quantification of the changes in cellular RI due to EMT. We induced prostate cancer cells to undergo EMT by exposing these cells to soluble Transforming Growth Factor Beta 1 (TGF-ß1). The biophysical characteristics of the cellular RI were quantified extensively in comparison to non-induced cancer cells. Our study shows promising clinical potential in utilizing the PC-TIR biosensing system not only to detect prostate cancer cells, but also to evaluate changes in prostate cancer cells due to EMT.

Novel route to size-controlled synthesis of MnFe2O4@MOF core-shell nanoparticles.

Nanoscale metal-organic framework (nMOF) is a distinctive type of crystalline compounds that consists of metal ions or clusters coordinated to organic ligands. This hybrid material has attracted fast-growing attention due to its tunable pore sizes, remarkably large surface areas, and high selectivity in uptaking small molecules. In this paper, we successfully developed a novel approach for synthesizing a core-shell structure with MIL-88B-4CH3 as a tunable nMOF shell and MnFe2O4 as a magnetic core. We controlled the growth of the core-shell particles by introducing different acetic acid concentrations and with varied reaction time. Acetic acid works as a modulating agent that allows for nucleation rate control, leading to tailored particle size. Our results show an increase in the particle size with increasing acetic acid concentration or reaction time. This study provides a valuable methodology for synthesis of core-shell nanoparticles with controlled sizes based on nMOF platforms.

Photoacoustic Imaging in Tissue Engineering and Regenerative Medicine.

Several imaging modalities are available for investigation of the morphological, functional, and molecular features of engineered tissues in small animal models. While research in tissue engineering and regenerative medicine (TERM) would benefit from a comprehensive longitudinal analysis of new strategies, researchers have not always applied the most advanced methods. Photoacoustic imaging (PAI) is a rapidly emerging modality that has received significant attention due to its ability to exploit the strong endogenous contrast of optical methods with the high spatial resolution of ultrasound methods. Exogenous contrast agents can also be used in PAI for targeted imaging. Applications of PAI relevant to TERM include stem cell tracking, longitudinal monitoring of scaffolds in vivo, and evaluation of vascularization. In addition, the emerging capabilities of PAI applied to the detection and monitoring of cancer and other inflammatory diseases could be exploited by tissue engineers. This article provides an overview of the operating principles of PAI and its broad potential for application in TERM. Impact statement Photoacoustic imaging, a new hybrid imaging technique, has demonstrated high potential in the clinical diagnostic applications. The optical and acoustic aspect of the photoacoustic imaging system works in harmony to provide better resolution at greater tissue depth. Label-free imaging of vasculature with this imaging can be used to track and monitor disease, as well as the therapeutic progression of treatment. Photoacoustic imaging has been utilized in tissue engineering to some extent; however, the full benefit of this technique is yet to be explored. The increasing availability of commercial photoacoustic systems will make application as an imaging tool for tissue engineering application more feasible. This review first provides a brief description of photoacoustic imaging and summarizes its current and potential application in tissue engineering.

Cellular Refractive Index Comparison of Various Prostate Cancer and Noncancerous Cell Lines via Photonic-Crystal Biosensor.

The current clinical standard for mass screening of prostate cancer are prostate-specific antigen (PSA) biomarker assays. Unfortunately, the low specificity of PSA's bioassays to prostate cancer leads to high false-positive rates, as such there is an urgent need for the development of a more specific detection system independent of PSA levels. In our previous research, we have successfully demonstrated, with the use of our Photonic-Crystal based biosensor in a Total-Internal-Reflection (PC-TIR) configuration, detection of prostate cancer (PC-3) cells against benign prostate hyperplasia (BPH-1) cells. The PC-TIR biosensor achieved detection of individual prostate cancer cells utilizing cellular refractive index (RI) as the only contrast parameter. To further study this methodology in vitro, we report a comprehensive study of the cellular RI's of various prostate cancer and noncancerous cell lines (i.e. RWPE-1, BPH-1, PC-3, DU-145, and LNCaP) via reflectance spectroscopy and single-cell RI imaging utilizing the PC-TIR biosensor. Our study shows promising clinical potential in utilizing the PC-TIR biosensor system for the detection of prostate cancer against noncancerous prostate epithelial cells.

Label-free in vitro prostate cancer cell detection via photonic-crystal biosensor.

Prostate-specific antigen (PSA) biomarker assays are the current clinical method for mass screening of prostate cancer. However, high false-positive rates are often reported due to PSA's low specificity, leading to an urgent need for the development of a more specific detection system independent of PSA levels. In our previous research, we demonstrated the feasibility of using cellular refractive indices (RI) as a unique contrast parameter to accomplish label-free detection of prostate cancer cells via variance testing, but were unable to determine if a specific cell was cancerous or noncancerous. In this paper, we report the use of our Photonic-Crystal biosensor in a Total-Internal-Reflection (PC-TIR) configuration to construct a label-free imaging system, which allows for the detection of individual prostate cancer cells utilizing cellular RI as the only contrast parameter. Noncancerous prostate (BPH-1) cells and prostate cancer (PC-3) cells were mixed at varied ratios and measured concurrently. Additionally, we isolated and induced PC-3 cells to undergo epithelial-mesenchymal transition (EMT) by exposing these cells to soluble factors such as TGF-01. The biophysical characteristics of the cellular RI were quantified extensively in comparison to non-induced PC-3 cells as well as BPH-1 cells. EMT is a crucial mechanism for the invasion and metastasis of epithelial tumors characterized by the loss of cell-cell adhesion and increased cell mobility. Our study shows promising clinical potential in utilizing the PC-TIR biosensor imaging system to not only detect prostate cancer cells, but also evaluate prostate cancer progression.

Transient extracellular application of gold nanostars increases hippocampal neuronal activity.

BACKGROUND: With the increased use of nanoparticles in biomedical applications there is a growing need to understand the effects that nanoparticles may have on cell function. Identifying these effects and understanding the mechanism through which nanoparticles interfere with the normal functioning of a cell is necessary for any therapeutic or diagnostic application. The aim of this study is to evaluate if gold nanoparticles can affect the normal function of neurons, namely their activity and coding properties. RESULTS: We synthesized star shaped gold nanoparticles of 180 nm average size. We applied the nanoparticles to acute mouse hippocampal slices while recording the action potentials from single neurons in the CA3 region. Our results show that CA3 hippocampal neurons increase their firing rate by 17% after the application of gold nanostars. The increase in excitability lasted for as much as 50 minutes after a transient 5 min application of the nanoparticles. Further analyses of the action potential shape and computational modeling suggest that nanoparticles block potassium channels responsible for the repolarization of the action potentials, thus allowing the cell to increase its firing rate. CONCLUSIONS: Our results show that gold nanoparticles can affect the coding properties of neurons by modifying their excitability.